A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib or trastuzumab, or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer

• Conditions: HER2-positive metastatic breast cancer who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting; MedDRA version: 13.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-019577-16-NO
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-31
• Last Update Posted: 9 October 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 525

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Signed written informed consent
2. Post-menopausal female subjects =18 years of age. Post-menopausal as defined
by any of the following:
• Age > 60 years
• Age = 45 years with amenorrhea > 12 months with an intact uterus
• Having undergone a bilateral oophorectomy or radiation castration with
amenorrhea for at least 6 months
• FSH and estradiol levels in postmenopausal range (utilizing ranges from the
local laboratory facility). In subjects who have previously been treated with
an GnRH/LHRH analogue, the last injection must have been administered >
4 months prior to randomization and menses must not have restarted
3. Histologically confirmed Stage IV invasive breast cancer
• Subjects may have either measurable or non-measurable disease per Response
Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer, 2009]
4. Tumors that are ER+ and/or PgR+ by local laboratory
5. Documentation of HER2 overexpression or gene amplification, in the invasive
component of either the primary tumor or metastatic disease site as defined as:
• 3+ by Immunohistochemistry (IHC)
and/or
• HER2/neu gene amplification by fluorescence, chromogenic or silver in situ
hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus
or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17
signals) of =2.0]
6. Subject must have received prior neoadjuvant and/or adjuvant trastuzumab
7. Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy
8. Subjects who have a life expectancy of > 6 months as assessed by the treating
investigator
9. Have baseline of Left Ventricular Ejection Fraction (LVEF) =50% measured by
echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
10. ECOG performance status of 0-1 (Section 12.2, Appendix 2)
11. All prior treatment related toxicities must be CTCAE (Version 4.0) = Grade 1
[NCI, 2009] at the time of randomization
12. Completion of screening assessments
13. Adequate baseline organ function defined by: (Refer to page 26 of Protocol)
French subjects: In France, a subject will be eligible for inclusion in this study only if
either affiliated to or a beneficiary of a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 185

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. History of another malignancy.
Exception: Subjects who have been disease-free for 5 years, or subjects with a
history of completely resected non-melanoma skin cancer or successfully treated
in situ carcinoma are eligible.
2. Subjects with extensive symptomatic visceral disease including hepatic
involvement and pulmonary lymphangitic spread of tumor, or the disease is
considered by the investigator to be rapidly progressing or life threatening
(subjects who are intended for chemotherapy)
3. Subjects who received prior chemotherapy, hormonal therapy, immunotherapy,
biologic therapy, or anti-HER2 therapy for advanced or metastatic disease
4. Serious cardiac illness or medical condition including but not confined to:
• Uncontrolled arrhythmias
• Uncontrolled or symptomatic angina
• History of congestive heart failure (CHF)
• Documented myocardial infarction <6 months from study entry
5. Known history of, or clinical evidence of, central nervous system (CNS)
metastases or leptomeningeal carcinomatosis
6. Current active hepatic or biliary disease (with exception of subjects with Gilbert's
syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment)
7. Concurrent disease or condition that may interfere with study participation, or any
serious medical disorder that would interfere with the subject’s safety (for
example, active or uncontrolled infection or any psychiatric condition prohibiting
understanding or rendering of informed consent)
8. Have any clinically significant gastrointestinal abnormalities that may alter
absorption such as malabsorption syndrome or major resection of the stomach or
bowels
9. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
drugs chemically related to any of the study agents or their excipients that, in the
opinion of the Investigator or GSK medical monitor, contraindicates their
participation
10. Any prohibited medication as described in Section 6.2.
11. Administration of an investigational drug within 30 days or 5 half-lives,
whichever is longer, preceding the first dose of study treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified